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Identification
NameNatalizumab
Accession NumberDB00108  (BIOD00083, BTD00083)
Typebiotech
Groupsapproved, investigational
Description

Humanized IgG4k monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to a4-integrin. Natalizumab was voluntarily withdrawn from U.S. market because of risk of Progressive multifocal leukoencephalopathy (PML). It was returned to market July, 2006.

Protein structureDb00108
Protein chemical formulaNot Available
Protein average weightNot Available
Sequences
Synonyms
SynonymLanguageCode
Anti-alpha4 integrinNot AvailableNot Available
Anti-VLA4Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TysabriElan Pharmaceuticals and Biogen Idec
Brand mixturesNot Available
Categories
CAS number189261-10-7
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor treatment of multiple sclerosis.
PharmacodynamicsIn multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells, and their counter-receptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be a secondary result of its blockade of the molecular interaction of a 4b 1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. α4-integrin is required for white blood cells to move into organs, therefore, natalizumab prevents these immune cells from crossing blood vessel walls to reach affected organs thereby decreasing inflamation.
Mechanism of actionBinds to the α4-subunit of α4b 1 and α4b 7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s).
AbsorptionNot Available
Volume of distribution
  • 5.7 ± 1.9 L [Multiple Sclerosis (MS) Patients]
  • 5.2 ± 2.8 L [Crohn’s Disease (CD) Patients]
Protein bindingNot Available
Metabolism

Most likely removed by opsonization via the reticuloendothelial system when bound to leukocytes.

Route of eliminationNot Available
Half life11 ± 4 days
Clearance
  • 16 +/- 5 mL/hour [patients with MS who did not have PML receiving the repeat IV administration of a 300 mg dose]
  • 22 +/- 22 mL/hour [Patients with Crohn’s Disease receiving the repeat IV administration of a 300 mg dose]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
Prices
Unit descriptionCostUnit
Tysabri 300 mg/15 ml vial207.31USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point61 °C (FAB fragment), 71 °C (whole mAb)Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)
References
Synthesis ReferenceNot Available
General Reference
  1. Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, Vyhnalek P, Zadorova Z, Palmer T, Donoghue S: Natalizumab for active Crohn’s disease. N Engl J Med. 2003 Jan 2;348(1):24-32. Pubmed
  2. Patent Information Link
External Links
ResourceLink
PharmGKBPA164747191
Drug Product Database2286386
RxListhttp://www.rxlist.com/cgi/generic/tysabri.htm
Drugs.comhttp://www.drugs.com/cdi/natalizumab.html
WikipediaNatalizumab
ATC CodesNot Available
AHFS Codes
  • 92:00.00
PDB Entries
FDA labelshow(96 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ado-trastuzumab emtansineAvoid combination due to the increased risk of infection.
BleomycinImmunosuppressants like bleomycin may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Brentuximab vedotinAvoid combination due to the increased risk of concurrent infection.
CanakinumabAvoid combination due to the increased risk of infection.
CarboplatinImmunosuppressants such as natalizumab may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
CarmustineImmunosuppressants such as carmustine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
Certolizumab pegolCo-administration with other TNF-blocking agents may increase the risk of serious infections. Concomitant therapy is not recommended.
ChlorambucilImmunosuppressants such as chlorambucil may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants.
CisplatinImmunosuppressants such as cisplatin may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
CladribineImmunosuppressants such as cladribine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
ClofarabineImmunosuppressants such as clofarabine may enhance the adverse/toxic effect of natalizumab. Specifically, the risk of concurrent infection may be increased. Patients receiving natalizumab should not use concurrent immunosuppressants, and patients receiving chronic corticosteroids prior to natalizumab should be tapered off of steroids prior to starting natalizumab.
golimumabAvoid combination due to the increased chance of infection.
HomoharringtonineAvoid combination due to the increased risk of infection.
PaclitaxelAvoid combination due to the increased risk of infection.
TacrolimusTacrolimus may increase the toxic/adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
TemozolomideThe immunosuppressant, Temozolomide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TemsirolimusTemsirolimus may increase the toxicity of Natalizumab. Concomitant therapy should be avoided.
TeniposideThe immunosuppressant, Teniposide, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TeriflunomideAvoid combination due to the increased risk of infection.
ThalidomideThalidomide may increase the adverse effects of Natalizumab. Concurrent administration should be avoided due to increased risk of infection.
ThiotepaThe immunosuppressant, Thiotepa, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TioguanineThe immunosuppressant, Thioguanine, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TofacitinibAvoid combination due to the increased risk of infection.
TopotecanThe immunosuppressant, Topotecan, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TositumomabThe immunosuppressant, Tositumomab, may increase the adverse effects of Natalizumab. Increased risk of Progressive Multifocal Leukoencephalopathy (PML) and other infections. Concurrent therapy should be avoided.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
TretinoinOral tretinoin may increase the adverse/toxic effects of Natalizumab. Concurrent therapy should be avoided.
ValrubicinValrubicin may increase Natalizumab toxicity. Concurrent therapy should be avoided.
VinblastineConcomitant Vinblastine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
VincristineConcomitant Vincristine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
VinorelbineConcomitant Vinorelbine and Natalizumab therapy may increase the risk of infection. Concurrent therapy should be avoided.
Food InteractionsNot Available

Targets

1. Integrin alpha-4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antibody

Components

Name UniProt ID Details
Integrin alpha-4 P13612 Details

References:

  1. Sheremata WA, Minagar A, Alexander JS, Vollmer T: The role of alpha-4 integrin in the aetiology of multiple sclerosis: current knowledge and therapeutic implications. CNS Drugs. 2005;19(11):909-22. Pubmed
  2. Niino M, Bodner C, Simard ML, Alatab S, Gano D, Kim HJ, Trigueiro M, Racicot D, Guerette C, Antel JP, Fournier A, Grand’Maison F, Bar-Or A: Natalizumab effects on immune cell responses in multiple sclerosis. Ann Neurol. 2006 May;59(5):748-54. Pubmed
  3. Stuve O, Bennett JL: Pharmacological properties, toxicology and scientific rationale for the use of natalizumab (Tysabri) in inflammatory diseases. CNS Drug Rev. 2007 Spring;13(1):79-95. Pubmed
  4. Craddock CF, Nakamoto B, Andrews RG, Priestley GV, Papayannopoulou T: Antibodies to VLA4 integrin mobilize long-term repopulating cells and augment cytokine-induced mobilization in primates and mice. Blood. 1997 Dec 15;90(12):4779-88. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Low affinity immunoglobulin gamma Fc region receptor III-B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-B O75015 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

3. Complement C1r subcomponent

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1r subcomponent P00736 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

4. Complement C1q subcomponent subunit A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit A P02745 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

5. Complement C1q subcomponent subunit B

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit B P02746 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

6. Complement C1q subcomponent subunit C

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Complement C1q subcomponent subunit C P02747 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

7. Low affinity immunoglobulin gamma Fc region receptor III-A

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor III-A P08637 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

8. High affinity immunoglobulin gamma Fc receptor I

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
High affinity immunoglobulin gamma Fc receptor I P12314 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

9. Low affinity immunoglobulin gamma Fc region receptor II-a

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-a P12318 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

10. Low affinity immunoglobulin gamma Fc region receptor II-b

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-b P31994 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

11. Low affinity immunoglobulin gamma Fc region receptor II-c

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Low affinity immunoglobulin gamma Fc region receptor II-c P31995 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

12. Intercellular adhesion molecule 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Intercellular adhesion molecule 1 P05362 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 29, 2010 14:34